| 31. |
- Soletormos, Gyorgy, et al.
(author)
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Design of Tumor Biomarker-Monitoring Trials : A Proposal by the European Group on Tumor Markers
- 2013
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In: Clinical Chemistry. - : Oxford University Press (OUP). - 0009-9147 .- 1530-8561. ; 59:1, s. 52-59
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Journal article (peer-reviewed)abstract
- A major application of tumor biomarkers is in serial monitoring of cancer patients, but there are no published guidelines on how to evaluate biomarkers for this purpose. The European Group on Tumor Markers has convened a multidisciplinary panel of scientists to develop guidance on the design of such monitoring trials. The panel proposes a 4-phase model for biomarker-monitoring trials analogous to that in use for the investigation of new drugs. In phase I, biomarker kinetics and correlation with tumor burden are assessed. Phase II evaluates the ability of the biomarker to identify, exclude, and/or predict a change in disease status. In phase III, the effectiveness of tumor biomarker guided intervention is assessed by measuring patient outcome in randomized trials. Phase IV consists of an audit of the long-term effects after biomarker monitoring has been included into standard patient care. Systematic well-designed evaluations of biomarkers for monitoring may provide a stronger evidence base that might enable their earlier use in evaluating responses to cancer therapy.
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| 32. |
- Starnberg, Karin, et al.
(author)
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Revision of the troponin T release mechanism from damaged human myocardium.
- 2014
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In: Clinical chemistry. - : Oxford University Press (OUP). - 1530-8561 .- 0009-9147. ; 60:8, s. 1098-104
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Journal article (peer-reviewed)abstract
- Cardiac troponin T (cTnT) is released from damaged heart tissue in patients with acute myocardial infarction. It is presumed that most cTnT is tightly bound and released following the degradation of myofibrils in necrotic cardiomyocytes, resulting in sustained increases in circulating cTnT. Evidence of a large irreversibly bound fraction is based on the inability to extract most cTnT from cardiac tissue in cold low-salt extraction buffers.
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| 33. |
- Ståhlberg, Anders, 1975, et al.
(author)
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Quantitative PCR Analysis of DNA, RNAs, and Proteins in the Same Single Cell.
- 2012
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In: Clinical chemistry. - : Oxford University Press (OUP). - 1530-8561 .- 0009-9147. ; 58:12, s. 1682-91
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Journal article (peer-reviewed)abstract
- The single cell represents the basic unit of all organisms. Most investigations have been performed on large cell populations, but understanding cell dynamics and heterogeneity requires single-cell analysis. Current methods for single-cell analysis generally can detect only one class of analytes.
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| 34. |
- Sävblom, Charlotta, et al.
(author)
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Genetic variation in KLK2 and KLK3 is associated with concentrations of hK2 and PSA in serum and seminal plasma in young men
- 2014
-
In: Clinical Chemistry. - : American Association for Clinical Chemistry. - 0009-9147 .- 1530-8561. ; 60:3, s. 490-499
-
Journal article (peer-reviewed)abstract
- BACKGROUND: Genetic variants in KLK2 and KLK3 have been associated with increased serum concentrations of their encoded proteins, human kallikrein-related peptidase 2 (hK2) and prostate-specific antigen (PSA), and with prostate cancer in older men. Low PSA concentrations in seminal plasma (SP) have been associated with low sperm motility. To evaluate whether KLK2 and KLK3 genetic variants affect physiological prostatic secretion, we studied the association of SNPs with hK2 and PSA concentrations in SP and serum of young, healthy men.METHODS: Leukocyte DNA was extracted from 303 male military conscripts (median age 18.1 years). Nine SNPs across KLK2-KLK3 were genotyped. We measured PSA and hK2 in SP and serum using immunofluorometric assays. The association of genotype frequencies with hK2 and PSA concentrations was tested with the Kruskal-Wallis test.RESULTS: Four KLK2 SNPs (rs198972, rs198977, rs198978, and rs80050017) were strongly associated with hK2 concentrations in SP and serum, with individuals homozygous for the major alleles having 3- to 7-fold higher concentrations than the intermediate concentrations found in other homozygotes and heterozygotes (all P < 0.001). Three of these SNPs were significantly associated with percentage of free PSA (%fPSA) in serum (all P < 0.007). Three KLK3 SNPs showed associations with PSA in SP, and the rs1058205 SNP was associated with total PSA in serum (P = 0.001) and %fPSA (P = 0.015).CONCLUSIONS: Associations observed in young, healthy men between the SP and serum concentrations of hK2 and PSA and several genetic variants in KLK2 and KLK3 could be useful to refine models of PSA cutoff values in prostate cancer testing.
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| 35. |
- Sävblom, Charlotta, et al.
(author)
-
Genetic Variation in KLK2 and KLK3 Is Associated with Concentrations of hK2 and PSA in Serum and Seminal Plasma in Young Men
- 2014
-
In: Clinical Chemistry. - : Oxford University Press (OUP). - 0009-9147 .- 1530-8561. ; 60:3, s. 490-499
-
Journal article (peer-reviewed)abstract
- BACKGROUND: Genetic variants in KLK2 and KLK3 have been associated with increased serum concentrations of their encoded proteins, human kallikrein-related peptidase 2 (hK2) and prostate-specific antigen (PSA), and with prostate cancer in older men. Low PSA concentrations in seminal plasma (SP) have been associated with low sperm motility. To evaluate whether KLK2 and KLK3 genetic variants affect physiological prostatic secretion, we studied the association of SNPs with hK2 and PSA concentrations in SP and serum of young, healthy men. METHODS: Leukocyte DNA was extracted from 303 male military conscripts (median age 18.1 years). Nine SNPs across KLK2-KLK3 were genotyped. We measured PSA and hK2 in SP and serum using immunofluorometric assays. The association of genotype frequencies with hK2 and PSA concentrations was tested with the Kruskal-Wallis test. RESULTS: Four KLK2 SNPs (rs198972, rs198977, rs198978, and rs80050017) were strongly associated with hK2 concentrations in SP and serum, with individuals homozygous for the major alleles having 3-to 7-fold higher concentrations than the intermediate concentrations found in other homozygotes and heterozygotes (all P < 0.001). Three of these SNPs were significantly associated with percentage of free PSA (% fPSA) in serum (all P < 0.007). Three KLK3 SNPs showed associations with PSA in SP, and the rs1058205 SNP was associated with total PSA in serum (P = 0.001) and % fPSA (P = 0.015). CONCLUSIONS: Associations observed in young, healthy men between the SP and serum concentrations of hK2 and PSA and several genetic variants in KLK2 and KLK3 could be useful to refine models of PSA cutoff values in prostate cancer testing. (C) 2013 American Association for Clinical Chemistry
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| 36. |
- Udell, J. A., et al.
(author)
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Inhibition of the Renin-Angiotensin System Reduces the Rise in Serum Aldosterone in Acute Coronary Syndrome Patients with Preserved Left Ventricular Function: Observations from the AVANT GARDE-TIMI 43 Trial
- 2013
-
In: Clinical Chemistry. - : Oxford University Press (OUP). - 0009-9147 .- 1530-8561. ; 59:6, s. 959-967
-
Journal article (peer-reviewed)abstract
- BACKGROUND: Acute coronary syndrome (ACS) activates neurohormonal pathways, including elevations in circulating aldosterone, with deleterious cardiovascular effects. We aimed to determine if early, more complete renin-angiotensin-aldosterone system inhibition (RAASI) in post-ACS patients without ventricular dysfunction or heart failure would result in a graded reduction in aldosterone concentrations.METHODS: We performed serial measurement of serum aldosterone within the Aliskiren and Valsartan to Reduce NT-proBNP via Renin-Angiotensin-Aldosterone-System Blockade (AVANT GARDE)/Thrombolysis in Myocardial Infarction (TIMI) 43 trial, a randomized double-blind, placebo controlled trial of RAASI by valsartan, aliskiren, or both in post-ACS patients with preserved ventricular function but increased natriuretic peptides. Aldosterone was measured at randomization and week 8.RESULTS: Median aldosterone concentrations were comparable across treatment arms at baseline (9.26 ng/dL; interquartile range 7.11-12.76; n = 1073). In the placebo group, there was a significant increase in aldosterone over 8 weeks (19.7% rise, 2.20 (0.36) ng/dL, P < 0.0001) that was significantly reduced across active RAASI therapies (1.36 (0.40) ng/dL with aliskiren; 1.02 (0.37) ng/dL with valsartan; and 0.85 (0.37) ng/dL with combination therapy, P trend = 0.008). Compared to placebo, RAASI monotherapy resulted in a pooled relative absolute aldosterone change of -1.01 (0.45) ng/dL (P = 0.026 vs placebo), and combination therapy resulted in a relative absolute aldosterone change of -1.35 (0.52) ng/dL (P = 0.01 vs placebo). No significant difference in aldosterone concentrations was achieved between dual vs single RAASI (P = 0.47).CONCLUSIONS: In ACS patients with preserved ventricular function but increased natriuretic peptides, serum aldosterone rises over time and is blunted by more complete RAASI. The clinical implications and role for RAASI in this population warrant further investigation.
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| 37. |
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| 38. |
- Venge, Per, et al.
(author)
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Cardiac Troponin Assay Classification by Both Clinical and Analytical Performance Characteristics : A Study on Outcome Prediction
- 2013
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In: Clinical Chemistry. - : Oxford University Press (OUP). - 0009-9147 .- 1530-8561. ; 59:6, s. 976-981
-
Journal article (peer-reviewed)abstract
- BACKGROUND: Cardiac troponin assays have been classified according to whether they measure the 99th percentile concentration of a healthy reference population with imprecision (expressed as CV) of <= 10%, between 10% and 20%, or >20%. Assays in these categories have been deemed "guideline acceptable," "clinically usable," or not acceptable," respectively. We compared four widely used "clinically usable" cardiac troponin I (cTnI) assays with an assay designated "not acceptable" for accuracy in predicting the clinical outcome of death. METHODS: Blood was collected from 259 men and 249 women, mean (SD) age 68.8 (17.8) and 70.2 (17.8) years, respectively, admitted to the emergency department for suspected myocardial infarction. We measured cTnI by the Access, Architect, i-Stat, Stratus CS, and VIDAS assays. Deaths in this population were recorded over a 31-month period. RESULTS: We found VIDAS cTnI assay measurement CVs of 10% and 20% at concentrations of 0.04 and 0.02 mu g/L, respectively. Comparing at the 10% CV cutoff concentration, VIDAS cTnI was less sensitive than the Access and Architect assays (P < 0.001) but more sensitive than i-Stat (P < 0.001) and Stratus CS (P < 0.001) in identifying patients with poor outcomes. At the 20% CV cutoff, the VIDAS assay was equivalent to the other assays in identifying patients with poor outcomes. CONCLUSIONS: For outcome prediction, the VIDAS cTnI assay was clinically equivalent or superior to other cTnI assays judged to be acceptable from a pure analytical standpoint. Thus, comparison of cardiac troponin assays should consider not only ana-lytical performance, but also clinical performance characteristics.
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| 39. |
- Wang, HY, et al.
(author)
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Profiling plasma microRNA in nasopharyngeal carcinoma with deep sequencing
- 2014
-
In: Clinical chemistry. - : Oxford University Press (OUP). - 1530-8561 .- 0009-9147. ; 60:5, s. 773-782
-
Journal article (peer-reviewed)abstract
- BACKGROUNDThe goal of this study was to establish a plasma microRNA profile by use of next-generation sequencing that could aid in assessment of patient prognosis in nasopharyngeal carcinoma (NPC).METHODSTwo panels of NPC patients and healthy controls (HCs) were recruited for this study. We used deep sequencing to screen plasma microRNAs. Differentially expressed microRNAs were verified by quantitative real-time PCR (qPCR). Kaplan–Meier survival analysis with the log-rank test was used to compare overall survival (OS) and progression-free survival (PFS) between groups.RESULTSTwenty-three plasma miRNAs with differential expression levels were selected for qPCR analysis on an independent set including 100 NPC patients and 55 HCs. NPC patients with low concentrations of miR-483–5p and miR-103 had better prognosis for 5-year OS than those with high concentrations (87.5% vs 55.8%, P < 0.001; 80.9% vs 62.3%, P = 0.031). Those with low concentrations of miR-29a and let-7c had poorer prognosis (54.8% vs 82.8%, P = 0.002; 56.3% vs 84.6%, P = 0.001). A 3-signature miRNA integrated with clinical stage was further identified in an independent set. We calculated a prognostic index score and classified patients into low-, medium-, and high-risk groups. Five-year OS among the 3 groups was significantly different (90.9%, 66.7%, and 23.8%; P < 0.001). By multivariate analysis, a high-risk score was the most significantly unfavorable prognostic factor independent of other clinical variables (P < 0.001, hazard ratio = 15.1, 95% CI = 5.2–43.9).CONCLUSIONSDifferentially expressed plasma miRNAs as identified by next-generation sequencing can be helpful for predicting survival in NPC patients.
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| 40. |
- Xu, Shengyuan, et al.
(author)
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Plasma Prolylcarboxypeptidase (Angiotensinase C) Is Increased in Obesity and Diabetes Mellitus and Related to Cardiovascular Dysfunction
- 2012
-
In: Clinical Chemistry. - : Oxford University Press (OUP). - 0009-9147 .- 1530-8561. ; 58:7, s. 1110-1115
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Journal article (peer-reviewed)abstract
- BACKGROUND: Prolylcarboxypeptidase (PRCP) (angiotensinase C) has 3 major targets, angiotensin II, prekallikrein, and alpha-melanocyte stimulating hormone(1-13). The truncation of the latter leads to loss in appetite regulation and obesity in experimental animals. The objectives of this study were to purify PRCP from a native source, establish a sensitive immunoassay for PRCP, and relate plasma PRCP concentrations to signs and symptoms of obesity, diabetes mellitus, and cardiovascular dysfunction.METHODS: Purification of PRCP from human neutrophils and establishment of a sensitive ELISA was carried out with the use of samples from study participants. Three cohorts were studied: healthy individuals (n = 40); a chest pain cohort (Fast Assessment of Thoracic Pain by Neural Networks) (n = 165); and a community-based cohort [Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS)] (n = 1004).RESULTS: PRCP was purified to homogeneity. Mean (SD) plasma concentrations in healthy individuals were 12.9 (3.2), mu g/L and were increased in patients with chest pain and in patients with obesity and/or diabetes mellitus (P < 0.0001). In the PIVUS cohort the concentrations were related to several measures of arterial plaque formation, thickness of arterial intima media and posterior wall of the heart (P = 0.04-0.000005); the Framingham score (r = 0.14, P < 0.0001); and concentrations of C-reactive protein (r = 0.16, P < 0.0001) and N-terminal pro B-type natriuretic peptide (r = -0.13, P < 0.0001).CONCLUSIONS: Plasma concentrations of PRCP may be used to reflect metabolic conditions in individuals with obesity and diabetes mellitus. The associations of PRCP concentrations with signs of cardiovascular dysfunction and cardiovascular abnormalities suggest a pivotal role of the enzyme in disease. (c) 2012 American Association for Clinical Chemistry
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